• Kristjan Linnet, Johann Agust Sigurdsson, Margret Olafia Tomasdottir, Emil Larus Sigurdsson, and Larus Steinthor Gudmundsson.
• Development Centre for Primary Healthcare in Iceland, Primary Health Care of the Capital Area, Reykjavik, Iceland kristjan.linnet@heilsugaeslan.is.
• BMJ Open. 2019 Dec 5; 9 (12): e033545.

ObjectivesTo assess the risk of mortality in primary care patients, multimorbid (≥2 chronic conditions) or not, prescribed hypnotics/anxiolytics.DesignA longitudinal cohort study SETTING: Primary healthcare in the Reykjavik area.Participants114 084 individuals (aged 10-79 years, average 38.5, SD 18.4) contacting general practitioners during 2009-2012 (mortality follow-up to 31 December 2016). Of those, the reference group comprised 58 560 persons who were neither multimorbid nor had redeemed prescriptions for hypnotics/anxiolytics. Participants (16 108) redeeming prescriptions for hypnotics/anxiolytics on a regular basis for 3 consecutive years were considered as consistent, long-term users. They were subdivided into low-dose (1-300 defined daily doses (DDD)/3 years), medium-dose (301-1095 DDDs/3 years) and high-dose users (>1095 DDDs/3 years). All six groups taking these drugs were compared with the reference group.Main Outcome MeasuresAll-cause mortality.ResultsHRs were calculated with the no multimorbidity-no drug group as a reference, using Cox proportional hazards regression model adjusting for age, sex and the number of chronic conditions (n=111 767), patients with cancer excluded. During follow-up, 516 358 person-years in total, 1926 persons died. Mean follow-up was 1685 days (4.6 years), range 1-1826 days (5.0 years). For all multimorbid patients who took no drugs the HR was 1.14 (95% CI 1.00 to 1.30) compared with those without multimorbidity. HRs in the non-multimorbid participants varied from 1.49 to 3.35 (95% CI ranging from 1.03 to 4.11) with increasing doses of hypnotics/anxiolytics, and correspondingly from 1.55 to 3.52 (1.18 to 4.29) in multimorbid patients.ConclusionsMortality increased in a dose-dependent manner among both multimorbid and non-multimorbid patients taking hypnotics/anxiolytics. This increase was clearly associated with prescribing of these drugs. Their use should be limited to the recommended period of 2-4 up to 6 weeks; long-term use may incur increased risk and should be re-examined.© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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